Effect of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8- yl)-1-propanone fumarate, a novel acetylcholinesterase inhibitor, on spatial cognitive impairment induced by chronic cerebral hypoperfusion in rats

It is of interest whether the acetylcholinesterase inhibitor, 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8- yl)-1-propanone fumarate (TAK-147), can improve cognitive impairment caused by chronic cerebral ischemia in rats. Two weeks after four-vessel occlusion, apparent impairments of spatial retrieval memory were observed in the Morris water maze. Both TAK-147 at doses of 0.1, 0.3 and 1.0 mg/kg and donepezil at doses of 0.3 and 1.0 mg/kg significantly ameliorated ischemia-induced memory deficits dose-dependently, but tacrine had no appreciable effect. Furthermore, we demonstrate that the intensity of staining by 2,3,5-triphenyltetrazolium in the hippocampal and cortical slices was significantly decreased by ischemia (10 min anoxia/aglycemia), and that it was also significantly restored by treatment with TAK-147 and donepezil.